Details

Autor(en) / Beteiligte

• Hillary, Robert F.
• Gadd, Danni A.
• McCartney, Daniel L.
• Shi, Liu
• Campbell, Archie
• Walker, Rosie M.
• Ritchie, Craig W.
• Deary, Ian J.
• Evans, Kathryn L.
• Nevado‐Holgado, Alejo J.
• Hayward, Caroline
• Porteous, David J.
• McIntosh, Andrew M.
• Lovestone, Simon
• Robinson, Matthew R.
• Marioni, Riccardo E.

Titel

Genome‐ and epigenome‐wide studies of plasma protein biomarkers for Alzheimer's disease implicate TBCA and TREM2 in disease risk

Ist Teil von

• Alzheimer's & dementia : diagnosis, assessment & disease monitoring, 2022, Vol.14 (1), p.e12280-n/a

Ort / Verlag

United States: John Wiley & Sons, Inc

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Introduction The levels of many blood proteins are associated with Alzheimer's disease (AD) or its pathological hallmarks. Elucidating the molecular factors that control circulating levels of these proteins may help to identify proteins associated with disease risk mechanisms. Methods Genome‐wide and epigenome‐wide studies (nindividuals ≤1064) were performed on plasma levels of 282 AD‐associated proteins, identified by a structured literature review. Bayesian penalized regression estimated contributions of genetic and epigenetic variation toward inter‐individual differences in plasma protein levels. Mendelian randomization (MR) and co‐localization tested associations between proteins and disease‐related phenotypes. Results Sixty‐four independent genetic and 26 epigenetic loci were associated with 45 proteins. Novel findings included an association between plasma triggering receptor expressed on myeloid cells 2 (TREM2) levels and a polymorphism and cytosine‐phosphate‐guanine (CpG) site within the MS4A4A locus. Higher plasma tubulin‐specific chaperone A (TBCA) and TREM2 levels were significantly associated with lower AD risk. Discussion Our data inform the regulation of biomarker levels and their relationships with AD.